ATF4 and plasma cell myeloma: Likewise, phosphorylation of eIF2α in response to proteasome inhibition in fibroblastic cell lines and multiple myeloma cells with either 26S proteasome inhibitors, MG132, or bortezomib is mediated by HRI (10, 17), and lack of HRI leads to impaired ATF4 signaling, which was previously shown to regulate autophagic flux downstream of eIF2α kinase (18).